SCC and the Medical Oncologist

This editorial looked at ways in which medical oncologists could become involved earlier in the management of aggressive SCCs of the skin. It comments on a paper in that issue of the journal which looked at using oral retinoids combined with Interferon injections 3 times a week with patients with severe aggressive or recurrent SCCs. Unfortunately they did no better than controls
The editorial is a useful summary. It can be viewed here
Randomized Trial of Adjuvant 13-cis-Retinoic Acid and Interferon Alfa for Patients With Aggressive Skin Squamous Cell CarcinomaAbenaa M. Brewster, J. Jack Lee, Gary L. Clayman, John L. Clifford, Mary Jo T. Necesito Reyes, Xian Zhou, Anita L. Sabichi, Sara S. Strom, Robert Collins, Christina A. Meyers, Scott M. Lippman

From the Departments of Clinical Cancer Prevention, Biostatistic and Applied Mathematics, Head and Neck Surgery, Thoracic/Head and Neck Medical Oncology, Epidemiology and Neuro-oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX; and the Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center and Feist-Weiller Cancer Center, Shreveport, LA

Address reprint requests to Scott M. Lippman, MD, Department of Thoracic and Head and Neck Medical Oncology, Unit 432, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77230-1439; e-mail: slippman@mdanderson.org

Purpose: To conduct a phase III trial of adjuvant 13-cis-retinoic acid (13cRA) plus interferon alfa (IFN-) for preventing tumor recurrence and second primary tumors (SPTs) of skin squamous cell carcinoma (SCC) among patients with aggressive skin SCC.

Patients and Methods: Sixty-six patients with aggressive skin SCC were randomly assigned to receive either 6 months of combined 13cRA (1 mg/kg/d orally) and IFN- (3 x 106 U subcutaneously three times per week) or no adjuvant therapy (control group) after SCC surgery and/or radiation.

Results: At 21.5 months median follow-up, treatment did not improve the time to tumor recurrence and SPT versus control (hazard ratio [HR], 1.13; 95% CI, 0.53 to 2.41), time to tumor recurrence (HR, 1.08; 95% CI, 0.43 to 2.72), or time to SPT (HR, 0.89; 95% CI, 0.27 to 2.93). Adjuvant 13cRA and IFN- was moderately tolerable; 29% of patients in the treatment arm required dose reductions for grade 3 or 4 toxicities.

Conclusion: Results of this phase III trial do not support 13cRA plus IFN- for adjuvant therapy of aggressive skin SCC. With high rates of tumor recurrence and SPTs, patients with aggressive skin SCC continue to have an unmet medical need, with devastating mortality, morbidity, and financial consequences. Promising agents with preclinical and early clinical results relevant to aggressive skin SCC deserve a high priority for future clinical drug development.

Margins for Dermatofibrosarcoma Protuberans

This article describes a prospective study of margins and number of attempts to achieve those margins in a group of patients with dermatofibrosarcoma protuberans.
Microscopic Margins and Results of Surgery for Dermatofibrosarcoma Protuberans.

RECONSTRUCTIVE

Plastic & Reconstructive Surgery. 119(6):1779-1784, May 2007.
Popov, Pentscho M.D.; Bohling, Tom M.D., Ph.D.; Asko-Seljavaara, Sirpa M.D., Ph.D.; Tukiainen, Erkki M.D., Ph.D.
Abstract:
Background: Dermatofibrosarcoma protuberans is a rare low-grade sarcoma of the skin with a tendency to recur locally after inadequate excision. Treatment has traditionally been wide excision with a 2- to 3-cm gross margin. Because of the variable results presented in mainly retrospective reports, it has been queried whether local control can be as good with conventional surgery as with micrographic surgery.

Methods: Forty patients with dermatofibrosarcoma protuberans treated by surgical excision were operated on at our center from 1987 to 2001. Data were recorded prospectively. Twenty-seven patients presented with a primary tumor and 13 with a locally recurrent tumor primarily operated on elsewhere. Gross and histologic margins were studied in detail.

Results: At a mean follow-up of 40 months, there were no recurrences. Thirty-four patients required single, five patients two, and one patient three operations before the margins were adequate (mean, 1.2 stages per patient). Twenty-three patients (58 percent) needed reconstructions. Tumor-free margins were obtained in 39 patients. The average thickness of surgical gross margins was 3.1 cm; histologically defined margins averaged 1.6 cm.

Conclusions: Good local control can be achieved with wide surgery. Histologic tumor-free margins differ greatly from gross margins and are difficult to assess clinically and macroscopically. Careful postoperative histologic examination with margins measured in millimeters should be carried out to define the adequacy of excision in all directions. On average, a 1.6-cm histologic margin was adequate for complete local control. Most patients can be operated on in one stage. Reconstructions are often needed.

Diagnostic Fluoroscopy and Skin damage

Fluoroscopy-Induced Chronic Radiation Skin Injury
A Disease Perhaps Often Overlooked Thomas H. Frazier, MD; Jeffrey B. Richardson, MD; Vilma C. Fabré, MD; Jeffrey P. Callen, MD


Arch Dermatol. 2007;143:637-640.

Background Fluoroscopy-induced chronic radiation dermatitis (FICRD) resulting from prolonged exposure to ionizing radiation during interventional procedures has been documented in the radiology and cardiology literature. However, the phenomenon has been rarely reported in the dermatologic literature. Since patients with FICRD often see a dermatologist or a primary care physician to treat their injuries, the diagnosis of FICRD is perhaps often overlooked.

Observations A 62-year-old man with type 2 diabetes mellitus and severe coronary artery disease was seen with a 2-year history of a pruritic, tender, telangiectatic patch lesion over his left scapula. Over the next 2 years, the lesion became indurated and eventually ulcerated. A skin biopsy specimen demonstrated changes consistent with a chronic radiation dermatitis. The patient was unaware of radiation exposure, but persistent questioning from his dermatologists revealed that he had undergone multiple fluoroscopy-guided cardiac procedures. This was confirmed by a review of his medical records.

Conclusion The diagnosis of FICRD should be considered for any patient who is seen with an acquired vascular lesion, a morphealike lesion, or an unexplained ulcer localized over the scapula, the back, or lateral trunk below the axilla.

Is the Siascope any value to Dermatologists for Real time melanoma screening?

Answer is not at all for this particular Dermatologist.The use of a spectrophotometric intracutaneous analysis device in the real-time diagnosis of melanoma in the setting of a melanoma screening clinicM.A. Haniffa, J.J. Lloyd**Regional Medical Physics Department, Royal Victoria Infirmary, Newcastle-upon-Tyne NE1 4LP, U.K. and C.M. LawrenceDepartment of Dermatology and *Regional Medical Physics Department, Royal Victoria Infirmary, Newcastle-upon-Tyne NE1 4LP, U.K.

Background Skin imaging devices to aid melanoma diagnosis have been developed in recent years but few have been assessed clinically.

Objectives To investigate if a spectrophotometric skin imaging device, the SIAscope, could increase a dermatologist's ability to distinguish melanoma from nonmelanoma in a melanoma screening clinic.

Methods Eight hundred and eighty-one pigmented lesions from 860 patients were prospectively assessed clinically and with the aid of the spectrophotometric device by a dermatologist. Assessment before and after spectrophotometric imaging was made and compared with histology, where available, or with the clinical diagnosis of a dermatologist with 20 years of experience.

Results One hundred and seventy-nine biopsies were performed, with 31 melanomas diagnosed. Sensitivity and specificity for melanoma diagnosis before and after spectrophotometry were 94% and 91% vs. 87% and 91%, respectively, with no significant difference in the area under the receiver operating characteristic curves (0·932 and 0·929).

Conclusions Our study provides no evidence for the use of SIAscope by dermatologists to help distinguish melanoma from benign lesions.

Chromosomal Features of Melanoma and Spitz Nevi.

This article shows the chromosomal differences between Spitz evi and Melanoma. It may be helpful in differentiating difficult histological cases some time in the future.(IMCC)
Genetic and epigenetic alterations in the differential diagnosis of malignant melanoma and spitzoid lesion
British Journal of Dermatology
Volume 156 Issue 6 Page 1287 - June 2007

M. Takata, J. Lin, S. Takayanagi, T. Suzuki**Laboratory Medicine, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390–8621, Japan, S. Ansai††Sapporo Institute for Dermatopathology, Sapporo, Japan, T. Kimura††Sapporo Institute for Dermatopathology, Sapporo, Japan, L. Cerroni‡‡Department of Dermatology, Medical University of Graz, Graz, Austria and T. SaidaDepartments of Dermatology and *Laboratory Medicine, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390–8621, Japan
†Sapporo Institute for Dermatopathology, Sapporo, Japan
‡Department of Dermatology, Medical University of Graz, Graz, Austria


Background The histopathological differentiation of malignant melanoma and Spitz naevus often presents diagnostic problems.

Objectives We aimed to find out applicable diagnostic parameters other than routine pathology.

Methods The cases included conventional melanomas and Spitz naevi as well as atypical spitzoid lesions that had posed diagnostic difficulties. We examined hotspots of mutation in the BRAF, NRAS and HRAS genes by polymerase chain reaction-based direct sequencing. We also analysed DNA copy number aberrations and the methylation of CpG sequences in several cancer-related genes by utilizing a novel methylation-specific multiplex ligation-dependent probe amplification method.

Results Twenty three of 24 conventional melanomas showed at least one of the genetic and epigenetic alterations examined, although one acral melanoma did not show any alteration. By sharp contrast, 12 Spitz naevi with an unambiguous histopathology showed no or few chromosomal aberrations, no oncogene mutations and no methylation of CpG sequences. Of the 16 ambiguous spitzoid lesions, most of which were designated atypical Spitz tumour by one of the authors, all but one showed no mutations, no methylations and few copy number aberrations. However, three tumours showed copy number loss of the cyclin-dependent kinase inhibitor 2A gene (CDKN2A), an alteration observed frequently in melanomas but not found in conventional Spitz naevi. These results show that, although most atypical Spitz tumours do not differ from conventional Spitz naevi showing virtually no genetic and epigenetic aberrations, some cases may have chromosomal aberrations that include copy number loss of the CDKN2A gene.

Conclusions Genetic and epigenetic analyses may be useful as an additional diagnostic tool to distinguish between melanoma and Spitz naevus, and may help to define subgroups in atypical Spitz tumours.

The nature of cutaneous metastases

Clinicopathologic correlation of cutaneous metastases
Sariya, D., et al. - To analyze the clinical, histopathologic, and immunohistochemical characteristics of skin metastases.
Cutaneous metastases can have variable clinical appearances and can mimic benign skin lesions. They are usually seen in patients with advanced disease, but they can be the presenting lesion. Although many metastatic adenocarcinomas can be recognized based on histologic findings alone, immunohistochemical analysis is an important diagnostic adjunct in some cases

Methodology
51 patients with biopsy-proven skin metastases and correlative clinical data.
4 dermatopathologists reviewed a random mixture of metastases and primary skin tumors.
Immunohistochemical studies for 12 markers were performed on the metastases, with skin adnexal tumors as controls.

Results
86% of the patients had known stage IV cancer, and skin metastasis was the presenting sign in 12%.
In 45% of the biopsies, the lesions were not suspected of being metastases owing to unusual clinical presentations.
76% of the patients died of disease (median survival, 5 months).
On pathologic review, many metastases from adenocarcinomas were either recognized or suspected, but the primary site was not easily identified based on histologic findings alone.
Metastases from small cell carcinomas and sarcomas were histologically misinterpreted as primary skin tumors.
Immunohistochemical analysis using a panel including p63, B72.3, calretinin, and CK5/6 differentiated metastatic carcinoma from primary skin adnexal tumors.

Why carry out Dermatoscopy?

A compilation of the discussion of this topic in the Archives and replies from Scott Menzies and Iris Zaludeck to a letter critical of their editorial can be found here

Distinguishing early melanoma histochemically.

This is an interesting paper that may point the way ahead in looking at distinguishing early melanoma from Clarke's (dysplastic) nevi. It may be useful in those more severly dysplastic histopathologically. Mind you most of us excise these fully anyway. Simply trying this test with a biopsy would not be the best thing to do!(IMCC)

Cyclooxygenase-2 (COX-2): first immunohistochemical marker distinguishing early cutaneous melanomas from benign melanocytic skin tumours.

ORIGINAL ARTICLES

Melanoma Research. 17(3):139-145, June 2007.
Chwirot, Barbara W.; Kuzbicki, Lukasz
Abstract:
We have reported recently that changes in expression level of COX-2 are correlated with development and progression of human melanoma. In this study, we investigated whether the COX-2 expression level might be a useful immunohistochemical marker for distinguishing cutaneous melanomas from benign melanocytic lesions. Up to now, immunohistochemical markers have not ensured satisfactory sensitivity and specificity of differential pathologic diagnosis of melanoma. The expression of COX-2 was determined immunohistochemically in formalin-fixed, paraffin-embedded specimens of 33 early Clark I/II melanomas and 58 naevi. Mean COX-2 expression in melanomas was significantly stronger than in naevi (P[almost equal to]10-13). A simple diagnostic algorithm using threshold values of the COX-2 expression level allows for differentiation between early melanomas and naevi with high sensitivity (Se) and specificity (Sp) (for Se between 91 and 100%, Sp values change between 96.5 and 51.7%). Areas under the receiver operating characteristic curves were, respectively, 0.97+/-0.02 and 0.86+/-0.04 for the COX-2 expression in central and border regions of the lesions. For all the melanomas (not only the early ones),the respective areas under the ROC curve values were 0.98+/-0.01 and 0.97+/-0.02. In conclusion, COX-2 is the first immunohistochemical marker that allows the distinguishing of early melanomas from benign melanocytic lesions with both high sensitivity and specificity.

Interventions for BCC

Interventions for basal cell carcinoma of the skin.Author(s): Bath-Hextall F; Perkins W; Bong J; Williams H;

BACKGROUND: Basal cell carcinoma (BCC) is the commonest skin cancer. BCCs
are slow-growing, locally invasive, epidermal skin tumours which mainly
affect white skinned people. The first line treatment is usually surgical
excision, but numerous alternatives are available. OBJECTIVES: To assess
the effects of treatments for basal cell carcinoma. SEARCH STRATEGY: We
searched the Cochrane Skin Group Specialised Register (January 2006),
the Cochrane Central Register of Controlled Trials (The Cochrane LIbrary
Issue 1, 2006), the Cochrane Database of Systematic Reviews (The Cochrane
Library Issue 1, 2006), MEDLINE (2004 to January 2006), EMBASE (2005 to
January 2006), the metaRegister of Controlled Trials (February 2006).
Cited references of all trials identified and key review articles were
searched. Pharmaceutical companies were contacted where appropriate for
reviews or unpublished trials. SELECTION CRITERIA: Inclusion criteria
were adults with one or more histologically proven, primary basal cell
carcinoma. The primary outcome measure was recurrence at three to five
years, measured clinically. The secondary outcome included early treatment
failure within six months, measured histologically. Adverse treatment
effects included aesthetic appearance and pain during and after treatment.
DATA COLLECTION AND ANALYSIS: Two authors independantly carried out study
selection and assessment of methodological quality. MAIN RESULTS: Twenty
seven studies were identified. Only one RCT of surgery versus radiotherapy
had primary outcome data at four years, showing significantly more persistent
tumours and recurrences in the radiotherapy group as compared to the surgery
group, (RR 0.09, 95%CI, 0.01 to 0.69). One study found no significant
difference for recurrence at 30 months when Moh's micrographic surgery
was compared to surgery for high risk facial BCCs, (RR 0.64, 95%CI 0.16,2.64).
One study of methylaminolevulinate photodynamic therapy (MAL PDT) versus
cryotherapy found no significant difference in recurrences in the MAL
PDT group when compared to cryotherapy at one year (RR 0.50, 95% CI 0.22,1.12).
Cryotherapy showed no significant difference in recurrences at one year
when compared to surgery on one small study. When radiotherapy was compared
to cryotherapy there were significantly fewer recurrences at one year
in the radiotherapy group compared to the cryotherapy group.Short-term
studies suggest a success rate of 87 to 88% for imiquimod in the treatment
of superficial BCC using a once-daily regimen for 6 weeks and a 76% treatment
response when treating nodular BCC for 12 weeks, when measured histologically.
AUTHORS' CONCLUSIONS: Overall there has been very little good quality
research on treatments for BCC. Most trials have only evaluated BCCs in
low risk locations. Surgery and radiotherapy appear to be the most effective
treatments with surgery showing the lowest failure rates. Although cosmetic
outcomes appear good with PDT, long term follow up data are needed. Other
treatments might have some use but few have been compared to surgery.
An ongoing study comparing imiquimod to surgery should clarify whether
imiquimod is a useful option.

Cochrane database of systematic reviews (Online: Update Software); 2007
1 1;(1)

Number of References: 63

Melanoma in Children

Melanoma in children and teenagers: an analysis of patients from the National Cancer Data Base.

Lange JR, Palis BE, Chang DC, Soong SJ, Balch CM.

Department of Surgery, Johns Hopkins Medicine, Baltimore, MD, USA jlange@jhmi.edu

PURPOSE: This study examines the demographics, presentation, and outcomes of children and teenagers with melanoma using a US hospital-based oncology database. PATIENTS AND METHODS: Data from the National Cancer Data Base from 1985 through 2003 were examined for demographics, presentation, and survival of patients aged 1 to 19 years, as well as a comparison group of patients aged 20 to 24 years. Two-sided linear and Pearson chi2 tests were calculated to examine associations. Proportions were compared using two-sided z tests. Five-year overall observed survival was evaluated using the Kaplan-Meier method and the log-rank test. Cox proportional hazards regression was used to estimate risk of mortality. RESULTS: Of 3,158 patients aged 1 to 19 years, 96.3% had cutaneous melanoma, 3.0% had ocular melanoma, and 0.7% had an unknown primary tumor. Cutaneous melanoma in patients aged 1 to 19 years was more common in girls (55.5%) and patients older than 10 years (90.5%). The demographics and presentation of cutaneous melanoma were age related; younger children were significantly more likely to be nonwhite and male and more likely to present with a head and neck primary tumors and with regional or distant metastases (linear chi2, P < .001 for sex, race, and extent of disease). Poorer survival was associated with higher stage and younger age. In contrast to patients aged 20 to 24 years, survival was not related to thickness in patients aged 1 to 19 years with localized invasive melanoma.
CONCLUSION: Melanoma in children and teenagers differs from melanoma in young adults in demographics, presentation, and survival. Further investigation is warranted to elucidate possible biologic correlates of the unique aspects of melanoma in children and teenagers.

Diet and Skin Cancer

This study from the Queensland group analysing data obtained during the Nambour study suggests that a high fat diet predisposes you to SCC but not BCC. Another explanation might be that people who eat high fat diets are not health conscious anyway and hence less likely to adopt sun safe behaviour. I have not read the whole article ,hence I do not know if they addressed this issue during their analysis of the two groups regarding their behaviour in the sun. I presume they had the same behavious or you would not have a valid study! If anyone knows Adele you might ask her.
Dietary pattern in association with squamous cell carcinoma of the skin: a prospective study
American Journal of Clinical Nutrition, Vol. 85, No. 5, 1401-1408, May 2007
Torukiri I Ibiebele, Jolieke C van der Pols, Maria Celia Hughes, Geoffrey C Marks, Gail M Williams and Adèle C Green
1 From the Cancer and Population Studies Group, Queensland Institute of Medical Research, Brisbane, Australia (TII, JCvdP, MCH, and ACG), and the School of Population Health, University of Queensland, Brisbane, Australia (JCvdP, GCM, and GMW)


Background: The role of diet in the development of skin cancer is inconclusive, and the effect of the combined consumption of foods has never been reported.

Objective: We prospectively investigated the association between dietary patterns and cutaneous basal cell (BCC) and squamous cell (SCC) carcinoma.

Design: Principal components analysis of 38 food groups was used to identify dietary patterns in 1360 adults aged 25–75 y who participated in a community-based skin cancer study in Nambour, Australia, between 1992 and 2002. We obtained baseline information about diet, skin color, and sun exposure factors. Multivariate-adjusted relative risks (RRs) for BCC and SCC tumors were estimated by using negative binomial regression modeling.

Results: Two major dietary patterns were identified: a meat and fat pattern and a vegetable and fruit pattern. The meat and fat pattern was positively associated with development of SCC tumors (RR = 1.83; 95% CI: 1.00, 3.37; P for trend = 0.05) after adjustment for confounders and even more strongly associated in participants with a skin cancer history (RR = 3.77; 95% CI: 1.65, 8.63; P for trend = 0.002) when the third and first tertiles were compared. A higher consumption of the vegetable and fruit dietary pattern appeared to decrease SCC tumor risk by 54% (P for trend = 0.02), but this protective effect was mostly explained by the association with green leafy vegetables. There was no association between the dietary patterns and BCC tumors.

Conclusion: A dietary pattern characterized by high meat and fat intakes increases SCC tumor risk, particularly in persons with a skin cancer history.

JAAD Melanoma Issue

The latest issue of JAAD has a series of articles that might interest bloggers including one challenging our ideas of the differences in distribution of melanomas in men and women the following link will take you to the Science Direct page for easy access to the abstracts of some of these articles.

Merkel cell Carcinoma

This is a rare condition. It is seldom diagnosed clinically. We are still working out the best way to treat it. A combined approach with wide excision and radiotherapy done immediately after the excision appears to be the best approach.

Radiotherapy for localised and advanced Merkel cell carcinoma of the skin: a single institution case series

European Journal of Dermatology. Volume 17, Number 3, 229-33, May-June 2007, Therapy


Author(s) : Falk Roeder, Robert Krempien, Florian Sterzing, Angela Funk, Martina Treiber, Jürgen Debus, Marc Bischof

Summary : Merkel cell carcinoma (MCC) is a rare malignant tumour of the skin with a tendency to rapid local progression, frequent spread to regional lymph nodes and distant metastases. We report results with radiotherapy in the treatment of MCC.Thirty-nine patients with histologically proven MCC were treated. Fifteen patients had stage I disease (12 primary, 3 recurrent tumours). Twenty-one patients had stage II disease (10 primary, 11 recurrent tumours). Thirty patients were treated with surgery and adjuvant radiotherapy. Six patients with inoperable disease received radiotherapy alone. Three patients in stage III with distant metastases were treated with palliative radiotherapy.For stage I patients, 3-year loco-regional control (LC), disease-specific survival (DSS) and overall survival (OS) rates were 90%, 100%, and 100%, respectively. For stage II patients, LC, DSS, and OS were 78%, 55%, and 29%, respectively. LC did not differ significantly between stage I and II patients. But, patients presented to radiotherapy directly after operation showed significantly improved LC compared to patients referred in recurrent situation (p \= 0.039). Two of six inoperable patients treated with radiotherapy alone relapsed locally.In the current study, surgery and immediate adjuvant radiotherapy resulted in strong loco-regional control. Radiotherapy alone is suggested only in inoperable or metastatic MCC.